INDICATIONS

small cell lung cancer sensitive disease after failure of
first-line chemotherapy. In clinical studies submitted to support approval,
sensitive disease was defined as disease responding to chemotherapy but
subsequently progressing at least 60 days (in the Phase 3 study) or at least 90
days (in the Phase 2 studies) after chemotherapy [seeClinical Studies].

HYCAMTIN in combination with cisplatin is indicated for
the treatment of:

Stage IV-B, recurrent, or persistent carcinoma of the
cervix which is not amenable to curative treatment with surgery and/or
radiation therapy.

DOSAGE AND ADMINISTRATION

Prior to administration of the first course of HYCAMTIN,
patients must have a baseline neutrophil count of > 1,500 cells/mm³ and a
platelet count of > 100,000 cells/mm³.

Ovarian Cancer And Small Cell Lung Cancer

Recommended Dosage

The recommended dose of HYCAMTIN is 1.5 mg/m² by
intravenous infusion over 30 minutes daily for 5 consecutive days, starting on
day 1 of a 21-day course.

In the absence of tumor progression, a minimum of 4
courses is recommended because tumor response may be delayed. The median time
to response in 3 ovarian clinical trials was 9 to 12 weeks, and median time to
response in 4 small cell lung cancer trials was 5 to 7 weeks.

Dosage Modification Guidelines

In the event of severe neutropenia (defined as < 500
cells/mm³) during any course, reduce the dose by 0.25 mg/m² (to 1.25 mg/m²) for
subsequent courses.

Alternatively, in the event of severe neutropenia,
administer G-CSF (granulocyte-colony stimulating factor) following the
subsequent course (before resorting to dose reduction) starting from day 6 of
the course (24 hours after completion of topotecan administration).

Cervical Cancer

Recommended Dosage

The recommended dose of HYCAMTIN is 0.75 mg/m² by intravenous
infusion over 30 minutes daily on days 1, 2, and 3; followed by cisplatin 50
mg/m by intravenous infusion on day 1 repeated every 21 days (a 21-day course).

Dosage Modification Guidelines

Dosage adjustments for subsequent courses of HYCAMTIN in
combination with cisplatin are specific for each drug. See manufacturer's prescribing
information for cisplatin administration and hydration guidelines and for
cisplatin dosage adjustment in the event of hematologic toxicity.

In the event of severe febrile neutropenia (defined as
< 1,000 cells/mm with temperature of 38.0°C or 100.4°F), reduce the dose of
HYCAMTIN to 0.60 mg/m² for subsequent courses.

Alternatively, in the event of severe febrile
neutropenia, administer G-CSF following the subsequent course (before resorting
to dose reduction) starting from day 4 of the course (24 hours after completion
of administration of HYCAMTIN).

If febrile neutropenia occurs despite the use of G-CSF,
reduce the dose of HYCAMTIN to 0.45 mg/m² for subsequent courses.

Dosage Adjustment In Specific Populations

Renal Impairment

No dosage adjustment of HYCAMTIN appears to be required
for patients with mild renal impairment (Clcr 40 to 60 mL/min). Dosage
adjustment of HYCAMTIN to 0.75 mg/m² is recommended for patients with moderate
renal impairment (20 to 39 mL/min). Insufficient data are available in patients
with severe renal impairment to provide a dosage recommendation for HYCAMTIN [see
Use In Specific Populations and CLINICAL PHARMACOLOGY].

HYCAMTIN in combination with cisplatin for the treatment
of cervical cancer should only be initiated in patients with serum creatinine
< 1.5 mg/dL. In the clinical trial, cisplatin was discontinued for a serum
creatinine > 1.5 mg/dL. Insufficient data are available regarding continuing
monotherapy with HYCAMTIN after cisplatin discontinuation in patients with cervical
cancer.

Handling

HYCAMTIN is a cytotoxic anticancer drug. Prepare HYCAMTIN
under a vertical laminar flow hood while wearing gloves and protective
clothing. If HYCAMTIN solution contacts the skin, wash the skin immediately and
thoroughly with soap and water. If HYCAMTIN contacts mucous membranes, flush
thoroughly with water.

Use procedures for proper handling and disposal of
anticancer drugs. Several guidelines on this subject have been published.1-4

Preparation and Administration

Each 4-mg vial of HYCAMTIN is reconstituted with 4 mL
Sterile Water for Injection. Then the appropriate volume of the reconstituted
solution is diluted in either 0.9% Sodium Chloride Intravenous Infusion or 5%
Dextrose Intravenous Infusion prior to administration.

Stability: Unopened vials of HYCAMTIN are stable
until the date indicated on the package when stored between 20° and 25°C (68°
and 77°F) [see USP] and protected from light in the original package.
Because the vials contain no preservative, contents should be used immediately
after reconstitution.

Reconstituted vials of HYCAMTIN diluted for infusion are
stable at approximately 20° to 25°C (68° to 77°F) and ambient lighting
conditions for 24 hours.